Impact of endothelial shear stress on coronary atherosclerotic plaque progression and composition: A meta-analysis and systematic review.

BACKGROUND AND AIMS: Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features. METHODS: A systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis. RESULTS: The meta-analysis encompassed 31'385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference -0.88, 95% CI -1.13 to -0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference -0.02, 95% CI -0.03 to -0.01) and fibrous plaque areas (mean difference -0.03, 95% CI -0.03 to -0.03). CONCLUSION: This meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making.

Impact of statin adherence and interruption within 6 months after ST-segment elevation myocardial infarction (STEMI): Results from the real-world regional registry FAST-STEMI.

BACKGROUND: The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real- world patients is understudied. AIMS: To identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up. METHODS: We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7 ± 1,6 years; 304 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature. RESULTS: From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI, whereas 3337 (58,1%) presented >80% adherence to statin therapy. Statin optimal adherence (>80%) resulted as protective factor towards both cardiovascular (0.1% vs 4.6%; AdjHR 0.025, 95%CI 0.008-0.079, p < 0.001) and all-cause mortality (0.3% vs 13.4%; Adj HR 0.032, 95%CI 0.018-0.059, p < 0.001) at 1 year follow-up. Further, a significant reduction of ischemic stroke incidence (1% vs 2.5%, p = 0.001) was seen in the optimal adherent group. Statin discontinuation within 6 months after STEMI showed an increase of both cardiovascular (5% vs 1.7%; AdjHR 2.23; 95%CI 1.37-3.65; p = 0,001) and all-cause mortality (14.8% vs 5.1%, AdjHR 2.32; 95%CI 1.73-3.11; p ã€ˆ0,001) at 1 year follow-up. After multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Age over 75 years old, chronic kidney disease, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence. CONCLUSIONS: n our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke.

Safety and efficacy of bempedoic acid: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND AND AIMS: Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia. METHODS: PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867). RESULTS: Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy. CONCLUSIONS: The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.

Role of Intracoronary Imaging in Myocardial Infarction with Non-Obstructive Coronary Disease (MINOCA): A Review.

Myocardial infarction with non-obstructive coronary artery disease occurs in 6% to 15% of all presentation of myocardial infarctions. The pathophysiologic mechanisms of MINOCA include epicardial vasospasm, coronary microvascular disorder, spontaneous coronary artery dissection, and coronary thrombus/embolism. The diagnosis is challenging, supported by intracoronary imaging with intravascular ultrasound (IVUS) and optical coherent tomography (OCT), coronary physiology testing, and cardiac magnetic resonance imaging (CMR). OCT is able to identify atherosclerotic causes of MINOCA (plaque erosion, plaque rupture, and calcified nodule) and nonatherosclerotic causes (spontaneous artery dissection, and spasm). In this review, we summarize the performance of the two intracoronary imaging modalities (IVUS and OCT) in MINOCA and discuss the importance of supplementing these modalities with CMR in order to drive target therapy.

Embolic Stroke of Undetermined Source: Role of Implantable Loop Recorder in Secondary Prevention.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most important cause of embolic stroke of undetermined source (ESUS). Implantable loop recorder (ILR) demonstrated the highest sensitivity for detecting it. This register was created to confirm the high prevalence of AF in patients after ESUS and to verify possible benefits on clinical outcomes such as TIA (Transient Ischaemic Attack)/stroke recurrence and death using ILR. METHODS: A total of 278 patients admitted to "Molinette" Hospital in Stroke Unit department between 2011 and 2016, diagnosed with ESUS, underwent ILR implantation if they had at least one risk factor for AF. A total of 165 patients admitted to other departments in the same center for the same pathology, without ILR, represent the control group. We used propensity score to select 132 patients from each group (matching age, sex, CHADS-VASC, and HAS-BLEED baseline characteristics). RESULTS: The detection rate of AF episodes was significantly higher in the ILR group (p < 0.001). No significant protective role of ILR for clinical endpoints was found on univariate analysis, although a trend towards significance has been pointed for the composite outcome of death and ischemic events recurrence (OR 0.52, CI 0.26-1.04, p = 0.06). A protective role of ILR was found for deaths (OR 0.4, CI 0.17-0.94, p 0.03) and for the composite outcome (OR 0.41, CI 0.19-0.87, p 0.02) on multivariate analysis in the best subsets. CONCLUSION: With our statistical models, we identified a significant clinical benefit from ILR monitoring, evidenced by a trend of less death and TIA/stroke recurrence and relevant ILR protection for prediction of TIA/stroke recurrence.